Affiliations 

  • 1 Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. Electronic address: wonfen@um.edu.my
  • 2 Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore
  • 3 Division of Cell Proliferation, Graduate School of Medicine, Tohoku University, Sendai, Japan
  • 4 Division of Biochemistry, Graduate School of Medicine, Tohoku University, Sendai, Japan
  • 5 Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 7 Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  • 8 Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore
  • 9 Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
Mol Immunol, 2015 Dec;68(2 Pt A):223-33.
PMID: 26350416 DOI: 10.1016/j.molimm.2015.08.012

Abstract

The Runx1 transcription factor cooperates with or antagonizes other transcription factors and plays essential roles in the differentiation and function of T lymphocytes. Previous works showed that Runx1 is expressed in peripheral CD4(+) T cells which level declines after T cell receptor (TCR) activation, and artificial deletion of Runx1 causes autoimmune lung disease in mice. The present study addresses the mechanisms by which Runx1 contributes to the maintenance of peripheral CD4(+) T cell quiescence. Microarray and quantitative RT-PCR analyses were employed to compare the transcriptome of Runx1 -/- CD4(+) T cells to those of unstimulated and TCR-stimulated Runx1 +/- cells. The results identified genes whose expression was modulated similarly by Runx1 deletion and TCR activation. Among them, genes encoding cytokines, chemokines, and Jak/STAT signaling molecules were substantially induced. In Runx1-deleted T cells, simultaneous increases in Il-17A and Rorγc, a known master gene in TH17 differentiation, were observed. In addition, we observed that the loss of Runx1 reduced the transcription of genes encoding quiescence-associated transcription factors, including Foxp1, Foxo1, and Klf2. Interestingly, we identified consensus Runx1 binding sites at the promoter regions of Foxp1, Foxo1, and Klf2 genes, which can be enriched by chromatin immunoprecipitation assay with an anti-Runx1 antibody. Therefore, we suggest that Runx1 may activate, directly or indirectly, the expression of quiescence-associated molecules and thereby contribute to the maintenance of quiescence in CD4(+) T cells.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.